The long-term objective of this project is the development of an exceptionally high yield, affinity-based cell separation technology. The technology has several valuable potential clinical applications. We will focus on the isolation of rare circulating neoplastic cells from blood. This technology will facilitate the development of a reproducible test for the detection of occult cancers at an early point in time, before metastases occur and when surgery could be curative.The limiting factor in capturing cells to a solid surface with antibodies is the number of attachment sites between a cell and the surface to which it is to be tethered. Increasing the number of links between the cell and the solid phase will be expected to increase the strength of attachment and the resulting cell yield. Our technology development program focuses on a method to logarithmically increase the number of attachment links. In this Phase I effort, we will develop two novel ligands that demonstrate extremely high densities of attachment to solid surfaces. We will conjugate these ligands to lymphocyte-specific antibodies and test their effectiveness. Specifically, we will measure the ability of these ligands to mediate a powerful attachment to the solid surface and compare them to conventional, existing affinity cell separation technologies